Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells
Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells
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DOI：
10.1016/j.lungcan.2020.05.023
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发表时间：
2020-08-01
期刊：
影响因子：
5.3
通讯作者：
Nishioka, Yasuhiko
中科院分区：
文献类型：
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作者：
Otsuka, Kenji;Mitsuhashi, Atsushi;Nishioka, Yasuhiko
背景：抗PD-1/PD-L1抗体联合化疗已被批准用于肺癌的一线治疗。然而，对恶性间皮瘤（MPM）的影响和化疗增强靶向PD-1/PD-L1在MPM.Materials和方法的效果的免疫学机制知之甚少：我们利用同系小鼠模型的MPM和肺癌和评估抗PD-1抗体的治疗效果和其与顺铂（CDDP）和培美曲塞（PEM）的组合。结果：抗PD-1抗体对MPM有明显的治疗作用。虽然这种效应与肿瘤中的CD 8（+）和CD 4（+）T细胞有关，但Foxp 3（+）细胞的数量并未减少，而是增加了。结论：抗PD-1抗体联合CDDP + PEM治疗MPM可能是通过抑制肿瘤内骨髓源性抑制细胞（MDSC）和血管的积聚，从而抑制肿瘤内血管生成，从而增强抗PD-1抗体的抗肿瘤作用。
Background: The combination of anti-PD-1/PD-L1 antibody with chemotherapy has been approved for the firstline therapy of lung cancer. However, the effects against malignant mesothelioma (MPM) and the immunological mechanisms by which chemotherapy enhances the effect of targeting PD-1/PD-L1 in MPM are poorly understood.Materials and Methods: We utilized syngeneic mouse models of MPM and lung cancer and assessed the therapeutic effects of anti-PD-1 antibody and its combination with cisplatin (CDDP) and pemetrexed (PEM). An immunological analysis of tumor-infiltrating cells was performed with immunohistochemistry.Results: We observed significant therapeutic effects of anti-PD-1 antibody against MPM. Although the effect was associated with CD8(+) and CD4(+) T cells in tumors, the number of Foxp3(+) cells was not reduced but rather increased. Consequently, combination with CDDP/PEM significantly enhanced the antitumor effects of anti-PD-1 antibody by decreasing numbers of intratumoral myeloid-derived suppressor cells (MDSCs) and vessels probably through suppression of VEGF expression by CDDP + PEM.Conclusions: The combination of anti-PD-1 antibody with CDDP + PEM may be a promising therapy for MPM via inhibiting the accumulation of MDSCs and vessels in tumors.